Chi-Hwa Yang

National Tsing Hua University, Hsinchu, Taiwan, Taiwan

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Publications (4)17.48 Total impact

  • Chia-Hua Lin, Chi-Hwa Yang, Yi-Rong Chen
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    ABSTRACT: UTF1 (undifferentiated embryonic cell transcription factor 1) is a marker for the pluripotency of embryonic stem cells. We found that UTF1-deficient clones, which were isolated from P19 embryonal carcinoma (EC) cells, showed higher neuron-differentiating potentials than the parental cell line. Consistent with this result, suppression of UTF1 expression in P19 cells by RNA interference enhanced retinoic acid (RA)-induced neuronal differentiation. Moreover, reconstitution of UTF1 expression in UTF1-deficient clones decreased their ability to undergo neuronal differentiation. Interestingly, the growth rates of UTF1-deficient P19 cells did not differ from that of parental cells in adherent cultures, but were increased in embryoid bodies during RA-induced differentiation. Furthermore, different from the parental cells, UTF1-deficient P19 clones could proceed to neuronal differentiation without forming embryoid bodies. Based on these results we proposed that endogenous UTF1 prevented P19 EC cells from neuronal differentiation, and that the loss of UTF1 directed EC cells toward the neuronal fate.
    The international journal of biochemistry & cell biology 11/2011; 44(2):350-7. · 4.89 Impact Factor
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    ABSTRACT: Vaccinia H1-related phosphatase (VHR) is classified as a dual specificity phosphatase. Unlike typical dual specificity phosphatases, VHR lacks the MAPK-binding domain and shows poor activity against MAPKs. We found that EGF receptor (EGFR) was a direct substrate of VHR and that overexpression of VHR down-regulated EGFR phosphorylation, particularly at Tyr-992 residue. Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR. Decreasing VHR expression by RNA interference caused higher EGFR phosphorylation at Tyr-992. In addition to EGFR, VHR also directly dephosphorylated ErbB2. Consistent with these results, suppression of VHR augmented the foci formation ability of H1299 non-small cell lung cancer (NSCLC) cells, whereas overexpression of VHR suppressed cell growth in both two- and three-dimensional cultures. Expression of VHR also suppressed tumor formation in a mouse xenograft model. Furthermore, VHR expression was significantly lower in NSCLC tissues in comparison to that in normal lung tissues. Collectively, this study shows that down-regulation of VHR expression enhances the signaling of ErbB receptors and may be involved in NSCLC pathogenesis.
    Journal of Biological Chemistry 01/2011; 286(12):10177-84. · 4.65 Impact Factor
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    ABSTRACT: Neuroendocrine-associated phosphatase (NEAP), an atypical dual specificity phosphatase is preferentially expressed in neuroendocrine cells. In this study we found that NEAP, but not NEAP-(C152S) mutant, evidently reduced epidermal growth factor (EGF) receptor (EGFR) downstream signaling, and impaired cell growth in response to EGF stimulation in PC12 cells. These phenomena were associated with NEAP-mediated down-regulation of EGFR mRNA and protein. NEAP had no significant effect on ErbB2/3 expression and phosphorylation levels in response to heregulin, indicating that the negative effect of NEAP on EGFR was selective. We showed that NEAP suppressed EGFR expression via decreasing the EGFR promoter activity and this was mediated through down-regulations of the Akt pathway and Wilms' tumor gene product (WT1). Consistent with these results, expression of WT1 reversed the suppressive effect of NEAP on EGFR promoter activity. Additionally, NEAP knockdown by RNA interference enhanced EGFR protein expression and nerve growth factor-induced differentiation, and an EGFR-specific inhibitor could reverse the later event. Taken together, our study indicated that NEAP modulates PC12 differentiation via suppression of EGFR expression and signaling.
    Journal of Neurochemistry 12/2008; 107(6):1544-55. · 3.97 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: The biochemical and biological properties of a novel neuroendocrine-associated phosphatase (NEAP) were characterized. NEAP had a sequence characteristic of a dual-specificity phosphatase (DSP), and was preferentially expressed in neuroendocrine cells/tissues as well as in skeletal muscle and heart. Expression of NEAP was up-regulated in nerve growth factor (NGF)-treated, differentiated PC12 cells. NEAP was cytosolic and did not apparently have effects against extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase activated by various stimuli. Although NEAP and MAPK phosphatase (MPK)-1 showed similar phosphatase activity towards p-nitro phenylphosphate (pNPP), in contrast to MKP-1, NEAP did not dephosphorylate JNK and p38-MAPK in vitro. Overexpression of NEAP, but not the C152S mutant, in PC12 cells suppressed NGF-induced phosphorylation of the p85 subunit of phosphatidylinositol 3-kinase (PI3K) and Akt activation. Overexpression of NEAP also suppressed neurite outgrowth induced by NGF and sensitized PC12 cells to cisplatin-induced apoptosis. Suppression of NEAP by RNA interference enhanced NGF-induced neurite outgrowth and Akt activation. Our results indicated that, unlike other DSPs, down-regulation of conventional MAPKs was not the major function of NEAP. Furthermore, NEAP might be involved in neuronal differentiation via regulation of the PI3K/Akt signaling.
    Journal of Neurochemistry 08/2006; 98(1):89-101. · 3.97 Impact Factor

Publication Stats

21 Citations
232 Views
17.48 Total Impact Points

Institutions

  • 2011
    • National Tsing Hua University
      • Institute of Molecular Medicine
      Hsinchu, Taiwan, Taiwan
  • 2006–2011
    • National Health Research Institutes
      • Institute of Biotechnology and Pharmaceutical Research
      Miao-li-chieh, Taiwan, Taiwan